Carbonic Anhydrase 9 mRNA/microRNA34a Interplay in Hypoxic Human Mammospheres.

Sabrina De Carolis, Sara Bertoni, Marina Nati, Laura D'Anello, Alessio Papi, Anna Tesei, Monica Cricca, Massimiliano Bonafé

Journal: Journal of cellular physiology 2016;231(7):1534-41

PMID: 26553365

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Abstract

The hypoxic environment is a crucial component of the cancer stem cell niche and it is capable of eliciting stem cell features in cancer cells. We previously reported that SNAI2 up-regulates the expression of Carbonic Anhydrase iso-enzyme 9 (CA9) in hypoxic MCF7 cells. Here we show that SNAI2 down-regulates miR34a expression in hypoxic MCF7 cell-derived mammospheres. Next, we report on the capability of miR34a to decrease CA9 mRNA stability and CA9 protein expression. We also convey that the over-expression of cloned CA9-mRNA-3'UTR increases the mRNA half-life and protein levels of two miR34a targets JAGGED1 and NOTCH3. The data here reported shows that the SNAI2-dependent down-regulation of miR34a substantially contributes to the post-transcriptional up-regulation of CA9, and that CA9-mRNA-3'UTR acts as an endogenous microRNA sponge. We conclude that CA9/miR34 interplay shares in the hypoxic regulation of mammospheres and therefore, may play a relevant role in the hypoxic breast cancer stem cell niche.

Address: Center for Applied Biomedical Research (CRBA), St. Orsola-Malpighi University Hospital, Bologna, Italy.; Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.; Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy.; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Biosciences Laboratory, Meldola, Italy.

DOI: 10.1002/jcp.25245